The potential role of intrinsic hypoxia markers as prognostic variables in cancer.

Tumor hypoxia is related to tumor progression and therapy resistance, which leads to poor patient outcome. It has been suggested that measuring the hypoxic status of a tumor helps to predict patient outcome and to select more targeted treatment. However, current methods using needle electrodes or exogenous markers have limitations due to their invasiveness or necessity for preinjection. Recent studies showed that hypoxia-regulated genes could be alternatively used as endogenous hypoxia markers. This is a review of 15 hypoxia-regulated genes, including hypoxia-inducible factor-1 and its targets, and their correlation with tumor hypoxia and patient outcome from 213 studies. Though most of the studies showed significance of these genes in predicting prognosis, there was no definitive prognostic and hypoxia marker. In conclusion, this review suggests the need for further studies with standardized methods to examine gene expression, as well as the use of multiple gene expressions.